Sheep erythropoietin (ESF), obtained from phenylhydrazine-treated and phlebotomized donors, will be infused into cross-matched adult sheep that are hemoglobin phenotype AA. The effectiveness of ESF will be determined in the same sheep under the following sequential conditions: 1) in the normal state; 2) after azotemia is created by subtotal nephrectomy; 3) after uremia is stabilized by hemodialysis; and 4) after androgen therapy in the dialyzed state. The response to identical amounts of ESF in the above conditions will be quantitated in vivo by ferrokinetics, reticulocyte response, and erythroid hemoglobin C synthesis, and in vitro by tissue culture techniques using the sheep's own normal and uremic marrow cells and plasma in the presenc of exogenous ESF. In addition, ESF serum half-life will be obtained in the above conditions after ESF infusions. The proposed studies should determine the effectiveness of endotoxin-free ESF in uremia, and whether inhibitors are present, and if so, whether hemodialysis modifies its effectiveness.